Elevated expression of proprotein convertases alters breast cancer cell growth in response to estrogen and tamoxifen

Two proprotein convertase cDNAs, PC1 and furin, were stably transfected into the human breast cancer cell line MCF-7. The PC1 or furin over-expressing cells possessed an altered morphology. When grown in vitro in a serum-free medium, the population doubling time of the convertase-transfected cells was twice that of wild-type (WT) cells. High concentrations of estradiol stimulated the growth of all three cell types to a similar extent; however, at low concentrations of estradiol, the convertase-transfected cells grew more slowly than WT cells. In athymic nude mice implanted with 5 mg estradiol pellets, the growth of tumors of convertase-transfected MCF-7 cells was stimulated to a degree similar to that of WT MCF-7 tumors. However, in mice implanted with lower-dose (1.5 mg) estradiol pellets, the tumors of PC1- or furin-transfected MCF-7 cells grew approximately five times slower than those of WT MCF-7 cells. In mice implanted with tamoxifen pellets, tumors of PC1- or furin-transfected MCF-7 cells regressed approximately five times slower than the WT tumors. This study shows that the over-expression of proprotein convertases confers a greater estrogen dependency and anti-estrogen resistance on human breast cancer cells.     

Is C-Reactive Protein a Prognostic Factor of Colorectal Cancer?

Purpose C-reactive protein, a commonly used inflammation marker, has been reported to be a prognostic factor of colorectal cancer. This prospective study was designed to confirm the prognostic value of its preoperative levels and to observe their perioperative change. Methods Between January 2001 and September 2005, preoperative C-reactive protein levels were obtained for 212 consecutive patients (140 males) receiving elective open resection of colorectal cancer. A level higher than 0.5 mg/dl was defined as positive. They were analyzed against clinicopathologic factors. The survival of 158 curative resections was analyzed. Postoperative levels (at months 1, 3, and 6) were collected for analysis of changing trend, from the patients receiving curative surgeries. Results Median value of preoperative C-reactive protein was 0.54 mg/dl (48.6 percent positive). Positive rate was significantly correlated with ulcerative type, larger size, higher stage, and positive carcinoembryonic antigen (>5 ng/ml). In both univariate log-rank test and multiple Cox proportional hazards regression, stage (univariate P = 0.011, and multivariate P = 0.016; hazard ratio, 6.23; 95 percent confidence interval, 1.41–27.54), C-reactive protein (0.5 mg/dl; P = 0.005, and P = 0.016; hazard ratio: 6.51; 95 percent confidence interval: 1.41–30.05), and differentiation (P = 0.006, and P = 0.043; hazard ratio, 3.53; 95 percent confidence interval, 1.04–11.98) were significant factors. Analysis of disease-free interval showed C-reactive protein was significant (P = 0.03): as level rose, prognosis worsened. The quiescent inflammation-response group (≤0.1 mg/dl) had excellent outcomes. Postoperatively, the C-reactive protein levels declined at the third postoperative month. Conclusions Preoperative C-reactive protein is an independent prognostic factor. The levels declined postoperatively, although with a lag. These findings seem to support the response hypothesis regarding C-reactive protein. Supported by Taipei Veterans General Hospital Grant 97.     

The dynamic process of adherence to a renal therapeutic regimen: Perspectives of patients undergoing continuous ambulatory peritoneal dialysis

Background

The nature of end-stage renal disease and the need for continuous ambulatory peritoneal dialysis require patients to manage various aspects of the disease, its symptoms and treatment. After attending a training programme, patients are expected to adhere to the renal therapeutic regimen and manage their disease with the knowledge and skills learned. While patients are the stakeholders of their health and related behaviour, their perceptions of adherence and how they adhere to their renal therapeutic regimen remains unexplored.

Aims

To understand adherence from patients’ perspectives and to describe changes in adherence to a therapeutic regimen among patients undergoing continuous ambulatory peritoneal dialysis.

Design

This study used a mixed methods design with two phases – a survey in phase I and semi-structured interviews in phase II. This paper presents phase II of the study.

Settings

The study was conducted at a renal unit of an acute hospital in Hong Kong.

Participants

Based on the phase I survey results, maximum variation sampling was employed to purposively recruit 36 participants of different genders (18 males, 18 females), ages (35–76 years), and lengths of dialysis experience (11–103 months) for the phase II interviews.

Methods

Data were collected by tape-recorded semi-structured interviews. Content analysis was employed to analyse the transcribed data. Data collection and analysis were conducted simultaneously.

Findings

Adherence was a dynamic process with three stages. At the stage of initial adherence, participants attempted to follow instructions but found that strict persistent adherence was impossible. After the first 2–6 months of dialysis, participants entered the stage of subsequent adherence, when they adopted selective adherence through experimenting, monitoring and making continuous adjustments. The stage of long-term adherence commenced after 3–5 years of dialysis, when participants were able to assimilate the modified therapeutic regimen into everyday life.

Conclusions

The process of adherence was dynamic as there were fluctuations at each stage of the participants’ adherence. With reference to each stage identified, nursing interventions can be developed to help patients achieve smooth transition throughout all the stages.     

Psychometric properties of the Chinese version of Sexual Function after Gynecologic Illness Scale (SFAGIS)

Purpose

This study aims to develop the Chinese version of the Sexual Function after Gynecologic Illness Scale (SFAGIS) and to establish its psychometric properties in Hong Kong Chinese patients with gynecological cancer.

Methods

A Chinese version of SFAGIS was developed using the Brislin model of translation and guidelines for cross-cultural adaptation of scales. The content validity and semantic equivalence were assessed by an expert panel. The translated version of SFAGIS was administered to 150 Hong Kong Chinese women with gynecological cancer to test the scale’s psychometric properties and to assess its feasibility. The convergent validity of the Chinese scale was tested by correlating it with the Chinese version of the sex relations subscale of the Psychosocial Adjustment to Illness Scale Self-Report (PAIS-SR).

Results

The average completion time for the Chinese SFAGIS was 16.2?±?6.6 min. The internal consistency of the Chinese SFAGIS was 0.93. Test–retest reliability was also high with an interclass correlation coefficient 0.76. A Pearson product–moment correlation found strong correlations among the Chinese SFAGIS and the Chinese version of the sex relations subscale of the PAIS-SR, indicating that both scales measure the same as or has a similar construct.

Conclusions

The Chinese version of SFAGIS is a reliable and valid instrument which can be used in clinical practice and research for assessing sexual function problems in Chinese patients with gynecological cancer and to identify those in need of attention.     

Ovarian ablation failures by radiation: a comparison of two dose schedules

Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.     

The Beagle Dog as an Animal Model for a Bioavailability Study of Controlled-Release Theophylline Under the Influence of Food

Beagle dogs were evaluated as an animal model to study the effect of food on the bioavailability of two commercially available oral controlled-release theophylline products. The products were administered with and without food in single doses, and the bioavailability parameters were compared with those following an i.v. aminophylline dose. The total plasma theophylline clearance in dogs following an i.v. dose was 0.128 liter/hr/kg and the volume of distribution was 0.8 liter/kg using a one-compartment model. The absolute bioavailabilities of these two products under fasting conditions were 31 and 48%, respectively. The food increased the bioavailability of one product and decreased the bioavailability of the other. The overall trends in relative bioavailability of these two products with and without food appeared to be similar to those reported in humans.     

Effect of splenectomy on morbidity and survival following curative gastrectomy for carcinoma

We performed a retrospective analysis of 392 patients who underwent curative resection of gastric adenocarcinoma to evaluate the impact of splenectomy on survival from gastric cancer and postoperative morbidity. Twelve factors, including splenectomy, were associated with a poor prognosis by univariate analysis. Multivariate analysis identified six of these factors, but not splenectomy, as independently predictive of death due to gastric cancer. The apparent adverse effect of splenectomy was due to its association with other significant risk factors. Postoperative complications occurred more commonly in patients who underwent splenectomy than in those who did not (45% vs 21%); patients in the splenectomy group also had a higher percentage of infectious complications than those in the nonsplenectomy group (75% vs 47%). We conclude that splenectomy has no direct influence on survival, but that it increases the morbidity of curative gastrectomy and should be avoided unless the spleen is close to or invaded by the tumor.     

Reduced Bioavailability of Moisture-Exposed Carbamazepine Resulting in Status Epilepticus

A 28-year-old man with seizures well controlled with carbamazepine (CBZ) and valproate (VPA) developed generalized convulsive status epilepticus three days after his CBZ tablets became wet during a rainstorm while he was camping out. He continued the CBZ but avoided ingesting obviously disintegrating tablets. The VPA was not exposed to excessive moisture. Previous random CBZ blood levels had been in the range of 9–13 μg/ml; at the time of admission to the emergency room the level had decreased to 3.8 μg/ml. The VPA level did not change significantly from baseline. The moistureexposed CBZ tablets were of expected weight but were swollen and enlarged. Analysis of these tablets by USP paddle method 2 demonstrated a mean dissolution of 16% at 60 min as compared with >80% for fresh CBZ tablets. After final dissolution of the moisture-exposed CBZ tablets, normal quantities of active drug were noted. We propose that poor dissolution of moisture-exposed CBZ tablets results in reduced bioavailability. We urge caution in the packaging and storage of CBZ to avoid exposure to moisture.